Preparation of Liposomal-encapsulated SOD and Serum Pharmacokinetics after Intravenous Administration

Liposomal-encapsulated superoxide dismutase (L-SOD) was prepared with a view to prolonging the half-life and pharmacodynamic action time. Presome® was adopted as a phospholipid in the preparation of L-SOD.L-SOD was sterilized through polycarbonate membrane filters having pore diameters of 0.2 μm and 0.4μm. The liposomal particle size, as measured by the dynamic light scattering method, was 198±40 nm. Effective SOD encapsulation efficiency was approximately 25.8%.Immediately after the i.v. injection of L-SOD into rats, blood levels of SOD decreased in a bi-exponential manner; the half-lives of the α-and β-phases were 16.6 minutes and 7.8 hours, respectively.AUC and MRT increased as compared with the i. v. injection of r-hSOD (free SOD), The SOD-activity in plasma was on a low level.These results suggested that still more L-SOD was trapped in the reticulo-endothelial system (RES), involving such organs as in the liver and spleen.In an effect to increase the SOD activity in plasma and prolong the circulation time of liposomes in blood, we prepared L-SOD modified with polyethyleneglycol derivatives (L-SOD/PEG. DOPE; L-SOD/PEG·DMG).After the i. v. injection of L-SOD/PEG·DOPE and L-SOD/PEG·DMG into rats, the SOD activity in plasma became higher and also the circulation time of liposomes in blood became longer as compared with the L-SOD i. v. injection.